Severe angioedema associated with tramadol use

SESSION TITLE: Drug Fiascos: Respiratory Compromise SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/09/2023 02:10 pm - 02:55 pm INTRODUCTION: Tramadol is a commonly used opioid analgesic that has been rarely associated with severe angioedema. CASE PRESENTATION: A 53-year-old male with known type 2 diabetes mellitus, end stage renal disease on dialysis, and allergies to sulfa drugs was admitted for management of fluid overload and acute hyperkalemia. He was managed with intravenous calcium gluconate and urgent dialysis. He also had right upper quadrant abdominal pain, which was investigated and attributed to biliary dyskinesia. On day 2 of his hospitalization, he was given a 50mg oral dose of tramadol for abdominal pain. Four hours later, he reported oral numbness and tingling, which was followed by rapid development of facial, oral, and laryngeal swelling. Of note, no other new drugs or allergens had been introduced in the past 16 hours. Vital signs at the time were a blood pressure of 136/90 mm Hg, heart rate 104/min, temperature of 97.8 degrees Fahrenheit, SpO2 94% on room air. Physical examination was notable for flushing, as well as significant oral and facial swelling. Hemoglobin was 10 g/dL, leukocytes 4.4 K/uL, potassium 4.6 mmol/L, creatinine 6.2 mg/dL. C1 esterase inhibitor was 39 mg/dL, functional C1 esterase inhibitor 102%, complement C2 2.9 mg/dL, complement C3 82 mg/dL, and complement C4 7 mg/dL.0.3mg intramuscular epinephrine, 50mg intravenous diphenhydramine, 4mg intravenous dexamethasone was administered. Rapid sequence intubation was performed, during which his airway was noted to be extremely edematous (Figure 1). The patient was then transferred to the intensive care unit and started on intravenous dexamethasone 10mg every 8 hours. Facial, oral, and airway swelling improved over time and a cuff leak was detectable 72 hours after intubation, at which point the patient was successfully extubated. Revisitation of medication allergies revealed a previous mild episode of facial and tongue swelling after administration of hydromorphone. Steroids were gradually tapered, and he was later discharged. DISCUSSION: Angioedema refers to the development of non-pitting subcutaneous edema secondary to vascular extravasation, commonly involving the upper respiratory and gastrointestinal tracts. It is largely understood to occur secondary to mast cell activation or excess accumulation of bradykinin. Mast cell activation can occur via allergic reactions or direct stimulation, while bradykinin accumulation is usually secondary to the use of angiotensin converting enzyme (ACE) inhibitors or hereditary/ acquired C1 inhibitor deficiency(1). Notably, there was no exposure to ACE inhibitors in this case and serum C1 inhibitor levels were within normal range. While full criteria for anaphylaxis were not met on initial assessment(2), it is possible that early intubation prevented the development of respiratory compromise and stridor. Opioids are known to be a potential cause of both direct and indirect (IgE mediated) mast cell activation, and there have been case reports describing tramadol induced angioedema(3). Treatment for angioedema includes airway assessment and protection; accompanying allergic/ anaphylactic signs or symptoms should prompt immediate administration of intramuscular epinephrine, systemic glucocorticoids, and anti-histamines. Bradykinin mediated angioedema typically requires specialized therapies (C1 inhibitor concentrate, icatibant, fresh frozen plasma). CONCLUSIONS: Tramadol may have the potential to cause rapid onset angioedema without accompanying urticarial symptoms. Reference #1: Kaplan AP. Angioedema. World Allergy Organ J. 2008 Jun 15;1(6):103–13. Reference #2: Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391–7. Reference #3: Hallberg P, Brenning G. Angioedema induced by tramadol--a potentially life-threatening condition. Eur J Clin Pharmacol. 2005 Feb;60(12):901–3. DISCLOSURES: No relevant relationships by Ibrahim Ahmed No relevant relationships by Mohammad Ahmed No relevant relationships by Jiannan Huang No relevant relationships by Swaminathan Perinkulam Sathyanarayanan